REVIEW ARTICLE Advances in science: next generation of lab tools, models and testing platforms used in predictive toxicology

Toxicology testing platforms are an integral part of the human health risk assessment process that determines whether an ingredient or fi nal formulation may induce harm to humans commensurate with accidental or intentional exposure. Th e process uses quantitative and qualitative methodologies that address hazard identifi cation, dose-response assessment, exposure assessment, and risk characterization. It is the paramount responsibility of manufacturers within their respective industry sector (pharmaceutical, personal care, etc.) to ensure the safety of their products within a framework with various levels of regulatory requirements. Historically, safety assessment has been performed using animal-based test methods (in vivo) that provide whole organism responses to toxicants. Th e toxicologist relied upon the animal tests to closely predict human response to hazards despite the imperfections introduced by inter-species extrapolations that are used to address the natural diff erences in anatomy and physiology. Due to the large number of products put on the market continuously, the requirement to protect public welfare by extensive evaluation of potential hazardous eff ects they may induce upon human exposure becomes a very challenging task. Th erefore, novel and more effi cient safety assessment methodologies need to be designed, evaluated and added to the predictive toxicology toolbox. We enter nowadays a modern scientifi c era that introduces Predictive Toxicology testing strategies encompassing a wide array of cutting edge methodologies that aim to reliably predict the human response to toxicants rather than observe the eff ects in animal-based test systems as in the classic toxicology approaches. Th e lab tools, models and testing platforms currently integrated in the fi eld of predictive toxicology can highlight areas where candidate molecules or prototypes may pose as hazardous at very early stages. Th us, they facilitate a quick and reliable selection process before further pre-clinical development and ultimately clinical trials are performed if and where applicable. Predictive toxicology refl ects a paradigm shift from in vivo testing methods and initially promoted a wide array of alternative methods ranging from simple monoculture test systems to more complex explants or reconstructed tissue models. Th ese available in vitro systems became instrumental for the investigation of cellular and molecular mechanisms underlying biological eff ects induced by exposure to toxicants. Furthermore, the combination between modern Abstract Toxicology testing platforms represent the basis of the human health risk assessment process that determines whether a material or product may induce harm to humans upon exposure. Historically, safety assessment of raw ingredients or finished formulations has been performed using animal-based test methods (in vivo) that provide whole organism responses to toxicants. Due to the large number of products launched by industry continuously, modern toxicology shifted in recent years towards the use of novel, fast and reliable alternative methods, ranging from in silico to in chemico or in vitro, of which some are validated for regulatory purposes. The manuscript also addresses emerging technologies in the form of “organ/body-on-a-chip” platforms which announce to be instrumental in allowing alternative systems to in vivo models to assess systemic toxic effects induced by chemicals.